AutologousTGFB1ModifiedCD34+StemCellsforRepairofDiabeticMacularEdemaandMacularIschemia Retinal vascular diseases, such as diabetic macular edema and macular ischemia remain a common cause of vision loss and blindness. Diabetes can damage the small blood vessels in the retina causing them to leak and occlude resultinginvisionloss.Althoughtreatmentsareavailableforaspectsofdiabeticoculardiseasenotherapyisavailable totreatthedamagedretinalvasculatureandischemicretina.Visionlossfromretinalischemiacanbeirreversible.A subgroup of DR patients suffers from macular ischemia and currently there is also no effective therapy. Research over the last decade has identified a class of bone marrow?derived circulating cells, CD34+ stem cells, which are capable of homing to vascular lesions and facilitating vascular repair. However, many diabetic patients have dysfunctionalCD34+stemcellswithnoreparativepotential.InthisSBIRFastTrackphasel/llproposalweuseanovel strategytocorrectdysfunctionaldiabeticCD34+cellsbytransientlymodifyingCD34+stemcellsderivedfrompatient blood that both restores perfusion to the ischemic retina and correct vessel leaking. Experiments from our NIH fundedstudiesshowthatthisCD34+dysfunctioncanbecorrectedbytransientlyinhibitingendogenoustransforming growth factor?? 1 (TGF??1) within the patient's own dysfunctional CD34+ stem cells using antisense phosphorodiamidatemorpholinooligomers(TGF?1PMO)toTGF?1.Ourproposedstudiesarefocusedaccordingto guidanceoftheFDA.In2012wecompletedapre?INDmeetingwiththeFDA.AmajorgoalistocompleteanINDin ordertobeginafirst?in?manclinicaltrial.Ourconcernindevelopingthisautologousstemcellapproachisthesafety ofthepatientandtheefficacyofthetherapy.Wehaveproposed5invitrophaselCD34+studiesand5phasellin vivo studies (including Akimba mice and diabetic baboons), testing safety and efficacy of our therapy. The investigatorsofthisapplicationincludeaveryexperiencedCEO,awell?knownpracticing/researchophthalmologist, aninternationalknownPMOexpertandaCD34+stemcellbiologist.